In 1976, Duffy got the role of Mark Harris in the television series The Man from Atlantis. Two years later, he got his big break in the role of Bobby Ewing on the TV series, Dallas, a role he played until 1991 (except for his notorious one-year absence from 1985 to 1986 that culminated in the surprise season finale where Duffy mysteriously reappeared in his wife Pam Ewing's shower; she had dreamed up his writing-off and the season after his "death"). During this time, he continued to hold a variety of roles in various TV specials.

On November 18, 1986, Duffy's parents, Terrance and Marie Duffy, were murdered by Kenneth Miller and Sean Wentz during the robbery of a Montana bar owned by Duffy's parents. Wentz and Miller, who were teenagers at the time, were convicted of the murders and sentenced to 180 years in prison. At the time, Duffy was criticized in the press for his seeming lack of sadness and grief over the deaths, but Duffy countered that his Buddhist beliefs (he converted from Roman Catholicism) meant that he believed they had moved on to a better place.

By the end of Dallas' run in 1991, Duffy switched to another popular television role, as the head of the Lambert family (alongside TV wife Suzanne Somers) on the family sitcom, Step by Step, a role which ran until the show's cancellation in 1998. Duffy continues to act in the occasional guest or voice acting appearance, including the shows Family Guy (in which he appeared once, in person, as Bobby Ewing with Victoria Principal's Pam), Justice League and Touched by an Angel. Duffy is married to Carlyn Duffy, and has two sons, Padraic and Conor, and the family has homes in Los Angeles and Oregon.

Most recently Patrick has starred in television movies Falling in Love With the Girl Next Door and Desolation Canyon.

He is an active Buddhist.

He is also the uncle of Oakland A's pitcher Barry Zito.

Duffy also attended the University of Washington in Seattle.